Phosphorylated α-Synuclein in Parkinson’s Disease
- 15 February 2012
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 4 (121), 121ra20
- https://doi.org/10.1126/scitranslmed.3002566
Abstract
Phosphorylated α-synuclein (PS-129), a protein implicated in the pathogenesis of Parkinson’s disease (PD), was identified by mass spectrometry in human cerebrospinal fluid (CSF). A highly sensitive and specific assay was established and used to measure PS-129 together with total α-synuclein in the CSF of patients with PD, other parkinsonian disorders such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and healthy individuals (a total of ~600 samples). PS-129 CSF concentrations correlated weakly with PD severity and, when combined with total α-synuclein concentrations in CSF, contributed to distinguishing PD from MSA and PSP. Further rigorous validation in independent cohorts of patients, especially those where samples have been collected longitudinally, will determine whether the concentration of PS-129 in CSF will be useful for diagnosing PD and for monitoring PD severity and progression.Keywords
This publication has 31 references indexed in Scilit:
- Complement 3 and Factor H in Human Cerebrospinal Fluid in Parkinson's Disease, Alzheimer's Disease, and Multiple-System AtrophyThe American Journal of Pathology, 2011
- Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progressionAnnals of Neurology, 2010
- Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formationJCI Insight, 2009
- Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegenerationExperimental Neurology, 2008
- Second consensus statement on the diagnosis of multiple system atrophyNeurology, 2008
- The phosphorylation state of Ser-129 in human α-synuclein determines neurodegeneration in a rat model of Parkinson diseaseProceedings of the National Academy of Sciences of the United States of America, 2008
- The Etiopathogenesis of Parkinson Disease and Suggestions for Future Research. Part IJournal of Neuropathology and Experimental Neurology, 2007
- Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s diseaseBiochemical and Biophysical Research Communications, 2006
- -Synuclein Phosphorylation Enhances Eosinophilic Cytoplasmic Inclusion Formation in SH-SY5Y CellsJournal of Neuroscience, 2005
- The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.Journal of Neurology, Neurosurgery & Psychiatry, 1988